A variety of poorly understood syndromes are associated with neonatal malabsorption and neonatal cholestasis. An understanding of the development of mechanisms for bile synthesis, secretion and turnover in the fetus and newborn is essential to the analysis of the pathogenesis of these syndromes. In previous grant periods we have examined the maturity of the liver and intestine relative to bile acid metabolism before and immediately after birth. Using techniques developed in this laboratory, we plan to explore this area further, to examine the ontogenesis of bile acid synthesis and secretion throughout the course of gestation, to identify factors which control the development of the system, and to attempt to accelerate its development in animals showing evidence of inadequate bile acid elaboration. It is expected that these studies will provide a more rational basis for the therapy of neonatal conditions associated with bile acid deficiency or retention.